Polycystin-1 surface localization is stimulated by polycystin-2 and cleavage at the G protein-coupled receptor proteolytic site.
Polycystin-1 surface localization is stimulated by polycystin-2 and cleavage at the G protein-coupled receptor proteolytic site.
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DOI：
10.1091/mbc.e10-05-0407
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发表时间：
2010-12
影响因子：
3.3
通讯作者：
Caplan MJ
中科院分区：
文献类型：
--
作者：
Chapin HC;Rajendran V;Caplan MJ
多囊蛋白（PC）1）定位于质膜需要与PC 2共表达，并在PC 1 G蛋白偶联受体蛋白水解位点裂解。这种效应既不需要PC 2的PC 1结合能力，也不需要其通道功能。多囊蛋白（PC）1和PC 2是与常染色体显性多囊肾病有关的膜蛋白。在PC 1的G蛋白偶联受体蛋白水解位点（GPS）的生理相关的裂解发生在分泌途径的早期。我们的研究结果表明，PC 2增加PC 1 GPS裂解和PC 1的外观在质膜。阻止PC 1的GPS裂解的突变阻止其质膜定位。PC 2是阳离子通道trp家族的成员，是重要的PC 1结合伴侣。PC 2对PC 1定位的影响独立于PC 2通道活性，如使用通道抑制PC 2突变所测试的。PC 1和PC 2可以通过它们的C-末端尾相互作用，但是去除任一蛋白的C-末端尾对人胚肾293细胞中的PC 1表面定位没有影响。极化LLC-PK细胞中的实验表明，顶端和纤毛PC 1定位需要PC 2，并且这种递送对PC 2截短敏感。总之，我们的工作表明，PC 2的表达是所需的运动的PC 1的质膜和睫状体膜。在成纤维细胞中，这种定位效应不依赖于PC 2的通道活性或PC 1结合能力，但涉及在PC 1蛋白的表面递送之前刺激PC 1的GPS切割。
The localization of polycystin (PC)1) to the plasma membrane requires coexpression with PC2 and cleavage at the PC1 G protein-coupled receptor proteolytic site. Neither the PC1 binding capacity of PC2 nor its channel function is required for this effect. Polycystin (PC)1 and PC2 are membrane proteins implicated in autosomal dominant polycystic kidney disease. A physiologically relevant cleavage at PC1's G protein-coupled receptor proteolytic site (GPS) occurs early in the secretory pathway. Our results suggest that PC2 increases both PC1 GPS cleavage and PC1's appearance at the plasma membrane. Mutations that prevent PC1's GPS cleavage prevent its plasma membrane localization. PC2 is a member of the trp family of cation channels and is an important PC1 binding partner. The effect of PC2 on PC1 localization is independent of PC2 channel activity, as tested using channel-inhibiting PC2 mutations. PC1 and PC2 can interact through their C-terminal tails, but removing the C-terminal tail of either protein has no effect on PC1 surface localization in human embryonic kidney 293 cells. Experiments in polarized LLC-PK cells show that apical and ciliary PC1 localization requires PC2 and that this delivery is sensitive to PC2 truncation. In sum, our work shows that PC2 expression is required for the movement of PC1 to the plasma and ciliary membranes. In fibroblast cells this localization effect is independent of PC2's channel activity or PC1 binding ability but involves a stimulation of PC1's GPS cleavage before the PC1 protein's surface delivery.